乳腺泌乳分化过程中能量和营养需求的增加会引起各种应激反应的上调，以支持细胞稳态。在这里，我们将干扰素基因刺激剂（STING）确定为小鼠乳腺上皮细胞（MEC）功能发育的免疫支持者。 MEC 分化的体外模型表明，STING 以不依赖于 cGAS 的方式被激活，以响应线粒体活性氧的积累而产生 I 型干扰素和促炎细胞因子。研究发现，STING 活性的诱导依赖于乳腺肿瘤抑制基因 single-thought 2 (SIM2)。使用小鼠哺乳模型，我们发现 STING 活性丧失会导致#3 乳腺提前退化，严重损害哺乳能力。我们的数据表明，STING 是乳腺成功功能分化所必需的，并且在 #3 乳腺和传统探索的腹股沟 4|9 对之间赋予不同的泌乳表型。这些发现证实了乳腺对的独特发育，这对于未来正常发育和乳腺癌发生的研究至关重要。© 2024。由 The Company of Biologies Ltd 出版。

Heightened energetic and nutrient demand during lactogenic differentiation of the mammary gland elicits upregulation of various stress responses to support cellular homeostasis. Here, we identify the stimulator of interferon genes (STING) as an immune supporter of the functional development of mouse mammary epithelial cells (MECs). An in vitro model of MEC differentiation revealed that STING is activated in a cGAS-independent manner to produce both type I interferons and proinflammatory cytokines in response to the accumulation of mitochondrial reactive oxygen species. Induction of STING activity was found to be dependent on the breast tumor suppressor gene single-minded 2 (SIM2). Using mouse models of lactation, we discovered that loss of STING activity results in early involution of #3 mammary glands, severely impairing lactational performance. Our data suggest that STING is required for successful functional differentiation of the mammary gland and bestows a differential lactogenic phenotype between #3 mammary glands and the traditionally explored inguinal 4|9 pair. These findings affirm unique development of mammary gland pairs that is essential to consider in future investigations into normal development and breast cancer initiation.© 2024. Published by The Company of Biologists Ltd.